Apparatus and methods for automatic adjustment of av interval to ensure delivery of cardiac resynchronization therapy

ABSTRACT

The disclosure provides methods and apparatus of left ventricular pacing including automated adjustment of a atrio-ventricular (AV) pacing delay interval and intrinsic AV nodal conduction testing. It includes—upon expiration or reset of a programmable AV Evaluation Interval (AVEI)—performing the following: temporarily increasing a paced AV interval and a sensed AV interval and testing for adequate AV conduction and measuring an intrinsic atrio-ventricular (PR) interval for a right ventricular (RV) chamber. Thus, in the event that the AV conduction test reveals a physiologically acceptable intrinsic PR interval then storing the physiologically acceptable PR interval in a memory structure (e.g., a median P-R from one or more cardiac cycles). In the event that the AV conduction test reveals an AV conduction block condition or if unacceptably long PR intervals are revealed then a pacing mode-switch to a bi-ventricular (Bi-V) pacing mode occurs and the magnitude of the AVEI is increased.

CROSS REFERENCE TO RELATED APPLICATIONS

This disclosure claims the benefit of provisional U.S. patentapplication Ser. No. 60/765,034 filed 3 Feb. 2006 and relates to anon-provisional U.S. Pat. No. 6,871,096 to Hill, entitled, “System andMethod for Bi-Ventricular Fusion-pacing;” a co-pending non-provisionalU.S. patent application by Pilmeyer and van Gelder; namely Ser. No.10/802,419 filed 17 Mar. 2004, and entitled, “APPARATUS AND METHODS FOR‘LEPARS’ INTERVAL-BASED FUSION-PACING;” a co-pending non-provisionalU.S. patent application by B. Ferek-Petric; namely Ser. No. 10/802,953filed 17 Mar. 2004, and entitled, “MECHANICAL SENSING SYSTEM FOR CARDIACPACING AND/OR FOR CARDIAC RESYNCHRONIZATION THERAPY,” a co-pendingnon-provisional U.S. patent application by Burnes and Mullen; namely,Ser. No. 10/803,570 filed 17 Mar. 2004, and entitled, “APPARATUS ANDMETHODS OF ENERGY EFFICIENT, ATRIAL-BASED BI-VENTRICULAR FUSION-PACING,”and pending application by Burnes filed 6 Dec. 2005 as U.S. Ser. No.11/295,272 entitled, “METHOD AND APPARATUS FOR OPTIMIZING PACINGPARAMETERS,” the entire contents of each of the foregoing is herebyincorporated by reference herein.

FIELD OF THE INVENTION

The invention pertains to cardiac resynchronization pacing systems. Inparticular, the invention relates to apparatus and methods forautomatically adjusting an AV interval during single ventricle pacing toefficiently deliver fusion-based cardiac resynchronization therapy (CRT)via ventricular pre-excitation. The invention can be configured tocompensate for cardiac conduction defects such as left or right bundlebranch block (LBBB, RBBB, respectively).

BACKGROUND OF THE INVENTION

In the above-referenced patent application to Hill, Hill discloses thatin certain patients exhibiting symptoms resulting from congestive heartfailure (CHF), cardiac output is enhanced by timing the delivery of anleft ventricular (LV) pacing pulse such that evoked depolarization ofthe LV is effected in fusion with the intrinsic depolarization of theright ventricle (RV). The fusion depolarization enhances stroke volumein such hearts where the RV depolarizes first due to intactatrio-ventricular (AV) conduction of a preceding intrinsic or evokedatrial depolarization wave front, but wherein the AV conducteddepolarization of the LV is unduly delayed. The fusion depolarization ofthe LV is attained by timing the delivery of the LV pace (LVp) pulse tofollow the intrinsic depolarization of the RV but to precede theintrinsic depolarization of the LV. Specifically, an RV pace (RVp) pulseis not delivered due to the inhibition of the RVp event upon the sensingof RV depolarization (RVs), allowing natural propagation of the wavefront and depolarization of the intraventricular septum, while an LVppulse is delivered in fusion with the RV depolarization.

However, due to a number of factors (e.g., the amount of time requiredfor appropriate signal processing, confounding conduction delays orconduction blockage of a patient, diverse electrode placement locations,and the like) for a variety of patients the system described may notalways effectively delivery CRT.

A need therefore exists in the art to efficiently and chronicallydelivery CRT to patients suffering from various cardiac conductionabnormalities who might not otherwise receive the benefits of CRTtherapy.

SUMMARY

Conventional cardiac resynchronization therapy (CRT) devices employ afixed programmable AV delay in combination with a rate adaptive AV delayfeature which adjusts the AV delay with sensed activity. The settingsfor the fixed AV delay and the rate adaptive AV feature are often leftat their nominal settings. In some patients the AV delay is programmedat rest to optimize mitral valve inflow (via echocardiography) oranother physiologic parameter. Recently, the inventors discovered thatfusion pacing (LV only pacing in which the LV pace is appropriatelytimed to the intrinsic conduction) provides acute physiologicoptimization similar to optimized bi-ventricular pacing. Based on thiscombination of findings, we hypothesize that an alternative means ofsetting the AV interval in bi-ventricular pacing may be equally orperhaps more effective than optimization at rest and generic rateadaptive AV adjustment based on activity sensor. In this disclosure,automatic adjustment of the AV interval for bi-ventricular pacing. Inone form of the invention, an implantable medical device (IMD)periodically (e.g., every 30 seconds) for example measures the intrinsicAV interval, maintains a buffer to track changes in the interval andadjusts the timing of the RV and LV pacing pulses to mirror thesechanges while maintaining pace capture of both ventricles.

According to the invention an automatic method for CRT devices to trackintrinsic AV interval and auto-adjust the pace timing of RV and LV tomirror such changes so that bi-ventricular pace capture is assured andthe AV intervals are adjusted with activity. The IMD extends the AVinterval to allow intrinsic ventricular conduction to break through.When an RV or LV sense is noted, a biventricular safety pace (Bi-VSP)could be issued. The AV interval will be recorded and added to a threeelement FIFO buffer. The A-RV pace interval will be set to the median ofthe 3 element buffer minus a predetermined RV pre-excitation interval(PEI). The A-LV pace interval will be set to the median of the threeelement buffer minus a predetermined LV pre-excitation interval (PEI).The PEIs can be programmable but we expect values of RVPEI=LVPEI=30 msto be reasonable nominal values which will be effective in a broad rangeof patients. The algorithm also includes a physiologic limiter whichwill govern how rapidly the AV interval is allowed to be changed (withthe intent of only tracking physiologically realistic changes). It alsoincludes minimum and maximum allowable values for AV intervals whichwill normally be fixed to nominals but could also be programmable. Manyof the features of the fusion pacing algorithms will also apply to thismode.

The invention provides a more simplified approach to delivery of CRT inwhich individualized optimization of AV intervals may no longer berequired. This method may be widely applicable to a broad range of CRTpatients. It offers a potential improvement in the rate adaptiveresponse of AV intervals in CRT patients. It offers a potentiallysuperior method of CRT in which intrinsic RV activation may be fusedwith both RV and LV paced activation wavefronts, resulting in aconsistent tri-focal activation of the ventricles.

For some patients suffering from heart failure and intra-ventricularconduction delays (e.g., LBBB, RBBB) the delivery of CRT may be affectedwith a single ventricular pacing stimulus by pre-exciting theconduction-delayed ventricle. Such a stimulus must be properly timedrelative to intrinsic depolarization of the other, non-delayedventricle. This phenomenon is referred to herein as a new, efficientform of “fusion-pacing” since ventricular activation from a pacingstimulus fuses or merges with ventricular activation from intrinsicconduction. When the ventricular pacing stimulus is properly timed adesired ventricular resynchronization results with a minimum of pacingenergy, thereby extending the operating life of an implantable pulsegenerator (e.g., an implantable cardioverter-defibrillator, pacemaker,and the like). Moreover, in some cases a more effective or physiologicform of CRT delivery can be achieved since the system and methods hereinutilize a portion of intrinsic activation, which can be superior to anentirely evoked (i.e., paced) form of CRT.

The challenge in such a system is determining the appropriate moment todelivery the single ventricular pacing stimulus, especially since suchtiming can be expected to vary with the timing dependent on thephysiologic status of the patient (e.g., exercise, medications etc). Inaddition to the foregoing, the inventors hereof have discovered a novelmeans of appropriately timing the ventricular pacing stimulus based onevaluation of at least one prior cardiac event. The inventors havediscovered that for some heart failure patients suffering fromintraventricular conduction delays such as left bundle branch block(LBBB) or right bundle branch block (RBBB), efficient delivery of CRTcan be achieved. According to the present invention, the triggering of asingle ventricular pacing stimulus occurs upon expiration of an AVinterval timed from at least one prior atrial event (paced or sensed;represented herein as “A_(p/s)”) and determined from at least one priorA_(p/s) that resulted in a sensed ventricular event (Vs). The triggeringevent, A_(p/s), can emanate from the right atrium (RA) or the leftatrium (LA) and the single ventricular pacing stimulus is timed topre-excite one ventricle so that intra-ventricular mechanical synchronyresults. The mechanical synchrony results from the fusing of the twoventricular depolarization wavefronts (i.e., one paced and the otherintrinsically-conducted).

According to the present invention, delivery of a single ventricularpacing stimulus occurs upon expiration of a fusion-AV or, hereinreferred to as the pre-excitation interval (“PEI”). One way to expressthis relationship defines the PEI as being based on an intrinsic AVinterval or intervals from an immediately prior cardiac cycle or cycles(AV_(n-1) or AV_(n-1), AV_(n-2), AV_(n-3), etc.). Thus, in this “form”of the invention PEI can be expressed as PEI=AV_(n-1)−V_(pei), whereinthe AV interval represents the interval from an A-event (A_(p/s)) to theresulting intrinsic depolarization of a ventricle (for a prior cardiaccycle) and the value of PEI equals the desired amount of pre-excitationneeded to effect ventricular fusion (expressed in ms). For a patientwith LBBB conduction status (for a current cardiac cycle “n”) the aboveformula can be expressed as: A-LVp_(n)=A-RV_(n-1)−LV_(pei) and for apatient suffering from RBBB conduction status the formula reduces to:A-RVp_(n)=A-LV_(n-1)−RV_(pei).

As noted above, the timing of the single ventricular pacing stimulus isan important parameter when delivering therapy according to the presentinvention. While a single, immediately prior atrial event (A_(p/s)) to aRV or an LV sensed depolarization can be utilized to set the PEI andderive the timing for delivering pacing stimulus (i.e., A-RV_(n-1) orA-LV_(n-1)) more than a single prior sensed AV interval, a prior PEI, aplurality of prior sensed AV intervals or prior PEIs can be utilized(e.g., mathematically calculated values such as a temporal derivedvalue, a mean value, an averaged value, a median value and the like).Also, a time-weighted value of the foregoing can be employed wherein themost recent values receive additional weight. Alternatively, the PEI canbe based upon heart rate (HR), a derived value combining HR with anactivity sensor input, P-wave to P-wave timing, R-wave to R-wave timingand the like. Again, these values may be time-weighted in favor of themost, or more, recent events. Of course, other predictive algorithmscould be used which would account for variability, slope or trend in AVinterval timing and thereby predict AV characteristics.

In another embodiment of the present invention, a data set optionallyconfigured as a look-up-table (LUT) correlating HR, activity sensorsignal input, and/or discrete physiologic cardiac timing intervals canbe used to set an appropriate PEI. If a mathematical derivation of HR isused to set the PEI, the data set or LUT can comprise at least two datasets or LUTs, one for stable or relatively stable HR, and another forvarious rate-of-change of the HR to more accurately reflect aphysiologic PEI. More generally, multiple LUTs may be utilized thatcorrelate to one or more physiologic parameters (e.g., contains PEIs forRV-only pacing, for LV-only pacing, for sensed atrial events, for pacedatrial events, or PEIs derived at least in part as a function of HR). Inthe latter embodiment, the present invention can be quickly reconfiguredto adapt to paroxysmal conduction blockage episodes, or so-calledconduction alternans (e.g., wherein cardiac conduction appears to mimicLBBB for some cardiac cycles and RBBB for others). In one refinement ofthe foregoing, the A-RVs or A-LVs interval, or series of intervals, usedto calculate the timing of the pre-excitation ventricular stimulationcan be divided into a pair of intervals, depending on whether the Aevent was a sensed, intrinsic atrial depolarization (As) event or anatrial pacing event (Ap).

Among other aspects of the present invention provides anenergy-efficient manner of providing single ventricle, pre-excitationfusion-pacing therapy. Heretofore, such pre-excitation was not possiblebecause in the prior art, the fusion-pacing stimulus was triggered by asensed event in the opposite chamber. In the case of fusion-pacingdelivered to the LV, a pacing stimulus is provided via at least oneelectrode disposed in electrical communication with a portion of the LV(e.g., an electrode deployed into a portion of the coronary sinus (CS),great vein, and branches thereof or epicardially). Since an evokeddepolarization from such electrode placement excites the myocardium fromthe opposite side of the ventricular wall (versus normal intrinsiccardiac excitation), the LV may need to be excited before an intrinsicsense (RVs) occurs for the same cycle to achieve optimal performance. Inone aspect, the present invention allows for dual chamber (atrial andventricular) CRT delivery which can be employed with a simple pair ofelectrical medical leads. The first lead operatively couples to anatrial chamber and the second lead operatively couples to a slow- orlate-depolarizing ventricular chamber, such as the LV. In this form ofthe invention, the lead disposed in communication with the ventricularchamber can be used for “far field” sensing of intrinsic ventriculardepolarizations. Optionally, a third lead may be used to sense intrinsicactivation in the opposite ventricular chamber or other part of the samechamber.

A variety of locations for the atrial lead can be used successfully inpracticing the methods of the present invention. For example, electricalcommunication (e.g., pacing and sensing an atrial chamber) with the RAcan utilize an epicardial or endocardial location and any appropriatesensing vector. Similarly, the intrinsic depolarization of the ventriclecan utilize any known sensing vector (e.g., tip-to-ring, coil-to-can,coil-to-coil, etc.). An endocardial location may include the common RApacing site of the RA appendage although RA septal or other locationsare acceptable. An electrode operatively coupled to the LA may also beused, including such locations as the CS and portions distal to the osof the CS, as well as the inter-atrial septal wall, among others. Thelocations at which the RV and LV leads couple with the myocardium canvary within each chamber, and depending on whether the patient has anRBBB or an LBBB will influence how this therapy is implemented toachieve intra-ventricular synchrony within the chamber where the bundlebranch block occurs. In the case of LBBB, a lead operatively coupled tothe RV is used to sense intrinsic depolarizations for determining thetiming needed for the operative pacing interval (e.g., A-LVP interval).This lead may be used in a variety of endocardial or epicardiallocations and more than one electrical lead and/or more than one pair ofpace/sense electrodes may be operatively coupled to a single cardiacchamber. With respect to endocardial locations, RV apical, RV outflowtract (RVOT), RV septal, RV free wall and the like will provide benefitsaccording to the present invention. In the case of RBBB, a lead can beoperatively positioned in or near the epicardium or endocardium of theLV for sensing intrinsic depolarizations used to determine the operativepacing timing.

For the purposes of this disclosure, an implementation for a patientwith a LBBB will be depicted and described; however, this exemplarydepiction is no way limiting for example, among others, that an RBBB ornonspecific bundle branch block implementation can be practiced. Forexample, the RBBB condition can be accommodated by simply monitoring LVconduction patterns by operatively coupling a sensing electrode to theLV and a pre-excitation pacing electrode to the RV (e.g., apex of theRV, RVOT, free wall, etc.). In addition to the number of pace/senseelectrodes employed, a variety of unipolar or bipolar sensing vectorsbetween electrodes may be implemented, including tip-to-ring,coil-to-can, coil-to-coil, and the like.

In terms of timing of the ventricular pacing stimulus, a measurement ofat least one prior A_(p/s)-RVs interval (from a paced or intrinsicatrial depolarization) provides a beginning point for determining anappropriate single-chamber pacing interval (e.g., A_(p/s)-LVp interval)that produces ventricular fusion. Furthermore, this algorithm can beexpanded so that multiple A-RVs intervals are measured and used tocalculate, or predict, a subsequent A_(p/s)-LVp. As mentionedhereinabove, time-weighted values of previous A-RVs may optionally beemployed to finalize an operational A_(p/s)-LVp value for the currentbeat. During delivery of a fusion-pacing therapy according to thepresent invention, the actual timing of LVp events and RVs events can bemonitored to confirm that the actual operating PEI equals (or isadequately close to) the desired or programmed LV_(pei).

Further addition, one or more mechanical, acoustic and/or activitysensors may be coupled to the heart and used to confirm that a desiredamount of bi-ventricular synchrony results from the delivered therapy.Some representative mechanical sensors for this purpose include fluidpressure sensors or acceleration sensors and the like. The mechanicalsensors operatively couple to the heart (e.g., LV lateral free-wall, RVseptal wall, epicardial RV locations, etc.). Output signals from suchsensors may be used to modify the timing of the fusion-pacing stimulus,especially during episodes such as a rapidly changing HR.

In addition to the therapy delivery aspects of the present invention, alimited number of therapy delivery guidance or security options may beused to determine if the pre-excitation fusion-pacing therapy ought tobe modified, initiated or discontinued. For example, in the event atransient conduction anomaly interrupting AV conduction is detected apacing modality switch to a double or triple chamber pacing modalitycould be implemented. In the event that the pre-excitation interval isshortened so much that a pacing stimulus occurs during the refractoryperiod of the ventricle—thereby causing loss of capture or potential forinducing an arrhythmia—fusion-pacing could cease or the operative pacinginterval could be lengthened (e.g., up to an amount approximately equalto the A-Vs interval of the other ventricle). If one of the sensorsindicates increasing ventricular asynchrony or decreasing hemodynamicresponse to the therapy, the atrial-based fusion-pacing therapy could bemodified or could cease. One such modification could be an adjustment ofthe amount of pre-excitation based on output from these sensors.Furthermore, from time-to-time the atrial-based fusion-pacing therapycould be suspended while cardiac activity is monitored so that anychange in normal sinus rhythm, or improvement in ventricular synchrony(e.g., desirable so-called “reverse remodeling”) can be accommodated. Inthe event that ventricular synchrony and conduction improves markedly,or that the suspension of CRT results in improved hemodynamics, a pacingmode switch from CRT to an atrial-based pacing mode such as AAI, ADI,AAI/R, ADI/R and the like may be implemented thereby providing a highlyefficient and physiologic pacing regime for the patient. Thereafter, inthe event that conduction anomalies cause ventricular asynchrony andresultant hemodynamic compromise or heart failure decompensation,another pacing mode switch can be implemented to resume an atrial-basedfusion-pacing mode according to the present invention.

The foregoing and other aspects and features of the present inventionwill be more readily understood from the following detailed descriptionof the embodiments thereof, when considered in conjunction with thedrawings, in which like reference numerals indicate similar structuresthroughout the several views.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an illustration of transmission of a normal cardiac conductionsystem through which depolarization waves are propagated through theheart in a normal intrinsic electrical activation sequence.

FIG. 2 is a schematic diagram depicting a three channel, atrial andbi-ventricular, pacing system for implementing the present invention.

FIG. 3 is a simplified block diagram of one embodiment of IPG circuitryand associated leads employed in the system of FIG. 2 for providingthree sensing channels and corresponding pacing channels thatselectively functions in an energy efficient, single-pacing stimulus,ventricular pre-excitation pacing mode according to the presentinvention.

FIG. 4 illustrates an embodiment of the energy efficient, single-pacingstimulus, ventricular pre-excitation pacing mode according to thepresent invention.

FIG. 5 illustrates an embodiment of the energy efficient, single-pacingstimulus, ventricular pre-excitation pacing mode according to thepresent invention.

FIG. 6 depicts a process for periodically ceasing delivery of thepre-excitation, single ventricular pacing therapy to determine thecardiac conduction status of a patient and performing steps based on thestatus.

DETAILED DESCRIPTION OF THE ILLUSTRATED EMBODIMENTS

In the following detailed description, references are made toillustrative embodiments for carrying out an energy efficient,single-pacing stimulus, ventricular pre-excitation pacing mode accordingto the present invention. It is understood that other embodiments may beutilized without departing from the scope of the invention. For example,the invention is disclosed in detail herein in the context of anintrinsically-based or AV sequential (evoked) uni-ventricular pacingsystem with dual ventricular sensing that operates in an atrialtracking, demand and/or triggered pacing modes. The present inventionprovides an efficient pacing modality for restoring electromechanicalventricular synchrony based upon either atrial-paced or atrial-sensedevents particularly for patients with some degree of either chronic,acute or paroxysmal ventricular conduction block (e.g.,intraventricular, LBBB, RBBB). Cardiac pacing apparatus, according tothe invention, are programmable to optionally operate as a dual- ortriple-chamber pacing system having an AV synchronous operating mode forrestoring upper and lower heart chamber synchronization and right andleft atrial and/or ventricular chamber depolarization synchrony. Asystem according to the invention efficiently provides cardiacresynchronization therapy (CRT) with a single ventricular stimulus percardiac cycle. In one embodiment, the inventive pacing system operatesin a V2DD or V2DD/R operating mode wherein intrinsic atrial eventsgovern the timing of the A-V2p pre-excitation interval. The foregoingnovel pacing codes are derived from the well-known NASPE pacing codeswherein the “V2” is intended to indicate that pacing stimulus isdelivered to the relatively late depolarizing ventricle (prior toactivation of the relatively more early depolarizing ventricle, or“V1”).

The present invention provides enhanced hemodynamic performance forpatients having intact AV nodal conduction but that nevertheless sufferfrom various forms of heart failure, ventricular dysfunctions and/orventricular conduction abnormalities. Pacing systems according to thepresent invention can also include rate responsive features andanti-tachyarrhythmia pacing and the like. In addition, a systemaccording to the invention may include cardioversion and/ordefibrillation therapy delivery.

In accordance with an aspect of the present invention, a method andapparatus is provided to mimic the normal depolarization-repolarizationcardiac cycle sequence of FIG. 1 and restore cardiac intra- and/orinter-ventricular synchrony between the RV, septum, and LV thatcontributes to adequate cardiac output related to the synchronizedelectromechanical performance of the RV and LV. The foregoing and otheradvantages of the invention are realized through delivery of cardiacpacing stimulation to the later depolarizing ventricle (V2) that aretimed to occur prior to a sensed depolarization in the other ventricle(V1). As a result of such timing, the V2 essentially is “pre-excited” sothat the electromechanical performance of V1 and V2 merge into a “fusionevent.” The amount pre-excitation may be individually selectable orautomatically determined. The amount of temporal pre-excitation can belinked to intrinsic propagation of cardiac excitation, which can changebased on a number of factors. For example, physiologic conduction delaythrough the A-V node or through the His-Purkinje fibers, electricalconduction delay for sensing intracardiac events (from electrodesthrough threshold sensing circuitry of a medical device), electricalconduction delay for pacing therapy delivery circuitry,electromechanical delay associated with the delivery of a pace and theensuing mechanical contraction, ischemic episodes temporarily temperingconduction pathways, myocardial infarction(s) zones, all candeleteriously impact cardiac conduction. Because the conduction statusof a patient can vary over time and/or vary based on other factors suchas heart rate, autonomic tone and metabolic status, the presentinvention provides a dynamically controllable single chamberresynchronization pacing modality. For example, based on one or more ofseveral factors, a pre-excitation optimization routine (or sub-routine)can be triggered so that a desired amount of single-chamber fusion-basedpacing ensues. Some of the factors include, (i) completion of a pre-setnumber of cardiac cycles, (ii) pre-set time limit, (iii) loss of captureof the paced ventricle (V2), and/or (iv) physiologic response triggers(e.g., systemic or intracardiac pressure fluctuation, heart rateexcursion, metabolic demand increase, decrease in heart wallacceleration, intracardiac electrogram morphology or timing, etc.). Thepresent invention provides a cardiac pacing system that can readilycompensate for the particular implantation sites of the pace/senseelectrode pair operatively coupled to the V2 chamber. When implementedin a triple-chamber embodiment, a pacing system according to the presentinvention can quickly mode switch in the event that a conduction defectappears in the non-pacing ventricle (V1) to either a true triple chamberbi-ventricular pacing mode (with or without CRT delivery) or to adedicated double chamber pacing mode (e.g., DDD/R or VVI and the like).

FIG. 2 is a schematic representation of an implanted, triple-chambercardiac pacemaker comprising a pacemaker IPG 14 and associated leads 16,32 and 52 in which the present invention may be practiced. The pacemakerIPG 14 is implanted subcutaneously in a patient's body between the skinand the ribs. The three endocardial leads 16,32,52 operatively couplethe IPG 14 with the RA, the RV and the LV, respectively. Each lead hasat least one electrical conductor and pace/sense electrode, and a remoteindifferent can electrode 20 is formed as part of the outer surface ofthe housing of the IPG 14. As described further below, the pace/senseelectrodes and the remote indifferent can electrode 20 (IND_CANelectrode) can be selectively employed to provide a number of unipolarand bipolar pace/sense electrode combinations for pacing and sensingfunctions, particularly sensing far field signals (e.g. far fieldR-waves). The depicted positions in or about the right and left heartchambers are also merely exemplary. Moreover other leads and pace/senseelectrodes may be used instead of the depicted leads and pace/senseelectrodes that are adapted to be placed at electrode sites on or in orrelative to the RA, LA, RV and LV. Also, as noted previously, multipleelectrodes and/or leads may be deployed into operative communicationwith the relatively “late” depolarizing ventricle to pace at multiplesites with varying degrees of pre-excitation. In addition, mechanicaland/or metabolic sensors can be deployed independent of, or in tandemwith, one or more of the depicted leads. In the event that multiplepacing electrodes are operatively deployed, a PEI for all suchelectrodes may be individually calculated. That is, a slightly differentamount of pre-excitation may be implemented for each discrete pacinglocation and said pre-excitation can thus be tuned for conductionanomalies (e.g., due to infarct or ischemia or the like).

The depicted bipolar endocardial RA lead 16 is passed through a veininto the RA chamber of the heart 10, and the distal end of the RA lead16 is attached to the RA wall by an attachment mechanism 17. The bipolarendocardial RA lead 16 is formed with an in-line connector 13 fittinginto a bipolar bore of IPG connector block 12 that is coupled to a pairof electrically insulated conductors within lead body 15 and connectedwith distal tip RA pace/sense electrode 19 and proximal ring RApace/sense electrode 21. Delivery of atrial pace pulses and sensing ofatrial sense events is effected between the distal tip RA pace/senseelectrode 19 and proximal ring RA pace/sense electrode 21, wherein theproximal ring RA pace/sense electrode 21 functions as an indifferentelectrode (IND_RA). Alternatively, a unipolar endocardial RA lead couldbe substituted for the depicted bipolar endocardial RA lead 16 and beemployed with the IND_CAN electrode 20. Or, one of the distal tip RApace/sense electrode 19 and proximal ring RA pace/sense electrode 21 canbe employed with the IND_CAN electrode 20 for unipolar pacing and/orsensing.

Bipolar, endocardial RV lead 32 is passed through the vein and the RAchamber of the heart 10 and into the RV where its distal ring and tip RVpace/sense electrodes 38 and 40 are fixed in place in the apex by aconventional distal attachment mechanism 41. The RV lead 32 is formedwith an in-line connector 34 fitting into a bipolar bore of IPGconnector block 12 that is coupled to a pair of electrically insulatedconductors within lead body 36 and connected with distal tip RVpace/sense electrode 40 and proximal ring RV pace/sense electrode 38,wherein the proximal ring RV pace/sense electrode 38 functions as anindifferent electrode (IND_RV). Alternatively, a unipolar endocardial RVlead could be substituted for the depicted bipolar endocardial RV lead32 and be employed with the IND_CAN electrode 20. Or, one of the distaltip RV pace/sense electrode 40 and proximal ring RV pace/sense electrode38 can be employed with the IND_CAN electrode 20 for unipolar pacingand/or sensing.

Further referring to FIG. 2, a bipolar, endocardial coronary sinus (CS)lead 52 is passed through a vein and the RA chamber of the heart 10,into the coronary sinus and then inferiorly in a branching vessel of thegreat cardiac vein to extend the proximal and distal LV CS pace/senseelectrodes 48 and 50 alongside the LV chamber. The distal end of such aCS lead is advanced through the superior vena cava, the right atrium,the ostium of the coronary sinus, the coronary sinus, and into acoronary vein descending from the coronary sinus, such as the lateral orposteriolateral vein.

In a four chamber or channel embodiment, LV CS lead 52 bears proximal LACS pace/sense electrodes 28 and 30 positioned along the CS lead body tolie in the larger diameter CS adjacent the LA. Typically, LV CS leadsand LA CS leads do not employ any fixation mechanism and instead rely onthe close confinement within these vessels to maintain the pace/senseelectrode or electrodes at a desired site. The LV CS lead 52 is formedwith a multiple conductor lead body 56 coupled at the proximal endconnector 54 fitting into a bore of IPG connector block 12. A smalldiameter lead body 56 is selected in order to lodge the distal LV CSpace/sense electrode 50 deeply in a vein branching inferiorly from thegreat vein GV.

In this case, the CS lead body 56 would encase four electricallyinsulated lead conductors extending proximally from the more proximal LACS pace/sense electrode(s) and terminating in a dual bipolar connector54. The LV CS lead body would be smaller between the LA CS pace/senseelectrodes 28 and 30 and the LV CS pace/sense electrodes 48 and 50. Itwill be understood that LV CS lead 52 could bear a single LA CSpace/sense electrode 28 and/or a single LV CS pace/sense electrode 50that are paired with the IND_CAN electrode 20 or the ring electrodes 21and 38, respectively for pacing and sensing in the LA and LV,respectively.

In this regard, FIG. 3 depicts bipolar RA lead 16, bipolar RV lead 32,and bipolar LV CS lead 52 without the LA CS pace/sense electrodes 28 and30 coupled with an IPG circuit 300 having programmable modes andparameters of a bi-ventricular DDDR type known in the pacing art. Inaddition, at least one physiologic sensor 41 is depicted operativelycoupled to a portion of myocardium and electrically coupled to a sensorsignal processing circuit 43. In turn the sensor signal processingcircuit 43 indirectly couples to the timing circuit 330 and via bus 306to microcomputer circuitry 302. The IPG circuit 300 is illustrated in afunctional block diagram divided generally into a microcomputer circuit302 and a pacing circuit 320. The pacing circuit 320 includes thedigital controller/timer circuit 330, the output amplifiers circuit 340,the sense amplifiers circuit 360, the RF telemetry transceiver 322, theactivity sensor circuit 322 as well as a number of other circuits andcomponents described below.

Crystal oscillator circuit 338 provides the basic timing clock for thepacing circuit 320, while battery 318 provides power. Power-on-resetcircuit 336 responds to initial connection of the circuit to the batteryfor defining an initial operating condition and similarly, resets theoperative state of the device in response to detection of a low batterycondition. Reference mode circuit 326 generates stable voltage referenceand currents for the analog circuits within the pacing circuit 320,while analog to digital converter ADC and multiplexer circuit 328digitizes analog signals and voltage to provide real time telemetry if acardiac signals from sense amplifiers 360, for uplink transmission viaRF transmitter and receiver circuit 332. Voltage reference and biascircuit 326, ADC and multiplexer 328, power-on-reset circuit 336 andcrystal oscillator circuit 338 may correspond to any of those presentlyused in current marketed implantable cardiac pacemakers.

If the IPG is programmed to a rate responsive mode, the signals outputby one or more physiologic sensor are employed as a rate controlparameter (RCP) to derive a physiologic escape interval. For example,the escape interval is adjusted proportionally the patient's activitylevel developed in the patient activity sensor (PAS) circuit 322 in thedepicted, exemplary IPG circuit 300. The patient activity sensor 316 iscoupled to the IPG housing and may take the form of a piezoelectriccrystal transducer as is well known in the art and its output signal isprocessed and used as the RCP. Sensor 316 generates electrical signalsin response to sensed physical activity that are processed by activitycircuit 322 and provided to digital controller/timer circuit 330.Activity circuit 332 and associated sensor 316 may correspond to thecircuitry disclosed in U.S. Pat. Nos. 5,052,388 and 4,428,378.Similarly, the present invention may be practiced in conjunction withalternate types of sensors such as oxygenation sensors, pressuresensors, pH sensors and respiration sensors, all well known for use inproviding rate responsive pacing capabilities. Alternately, QT time maybe used as the rate indicating parameter, in which case no extra sensoris required. Similarly, the present invention may also be practiced innon-rate responsive pacemakers.

Data transmission to and from the external programmer is accomplished bymeans of the telemetry antenna 334 and an associated RF transceiver 332,which serves both to demodulate received downlink telemetry and totransmit uplink telemetry. Uplink telemetry capabilities will typicallyinclude the ability to transmit stored digital information, e.g.operating modes and parameters, EGM histograms, and other events, aswell as real time EGMs of atrial and/or ventricular electrical activityand Marker Channel pulses indicating the occurrence of sensed and paceddepolarizations in the atrium and ventricle, as are well known in thepacing art.

Microcomputer 302 contains a microprocessor 304 and associated systemclock 308 and on-processor RAM and ROM chips 310 and 312, respectively.In addition, microcomputer circuit 302 includes a separate RAM/ROM chip314 to provide additional memory capacity. Microprocessor 304 normallyoperates in a reduced power consumption mode and is interrupt driven.Microprocessor 304 is awakened in response to defined interrupt events,which may include A-TRIG, RV-TRIG, LV-TRIG signals generated by timersin digital timer/controller circuit 330 and A-EVENT, RV-EVENT, andLV-EVENT signals generated by sense amplifiers circuit 360, amongothers. The specific values of the intervals and delays timed out bydigital controller/timer circuit 330 are controlled by the microcomputercircuit 302 by means of data and control bus 306 from programmed-inparameter values and operating modes. In addition, if programmed tooperate as a rate responsive pacemaker, a timed interrupt, e.g., everycycle or every two seconds, may be provided in order to allow themicroprocessor to analyze the activity sensor data and update the basicA-A, V-A, or V-V escape interval, as applicable. In addition, themicroprocessor 304 may also serve to define variable AV delays and theuni-ventricular, pre-excitation pacing delay intervals (A-V2p) from theactivity sensor data, metabolic sensor(s) and/or mechanical sensor(s).

In one embodiment of the invention, microprocessor 304 is a custommicroprocessor adapted to fetch and execute instructions stored inRAM/ROM unit 314 in a conventional manner. It is contemplated, however,that other implementations may be suitable to practice the presentinvention. For example, an off-the-shelf, commercially availablemicroprocessor or microcontroller, or custom application-specific,hardwired logic, or state-machine type circuit may perform the functionsof microprocessor 304.

Digital controller/timer circuit 330 operates under the general controlof the microcomputer 302 to control timing and other functions withinthe pacing circuit 320 and includes a set of timing and associated logiccircuits of which certain ones pertinent to the present invention aredepicted. The depicted timing circuits include URI/LRI timers 364, V-Vdelay timer 366, intrinsic interval timers 368 for timing elapsedV-EVENT to V-EVENT intervals or V-EVENT to A-EVENT intervals or the V-Vconduction interval, escape interval timers 370 for timing A-A, V-A,and/or V-V pacing escape intervals, an AV delay interval timer 372 fortiming the A-LVP delay (or A-RVP delay) from a preceding A-EVENT orA-TRIG, a post-ventricular timer 374 for timing post-ventricular timeperiods, and a date/time clock 376.

According to the invention, the AV delay interval timer 372 is loadedwith an appropriate delay interval for the V2 chamber (i.e., either anA-RVP delay or an A-LVP delay as determined by the flow chart depictedat FIG. 4 and FIG. 5) to time-out starting from a preceding A-PACE orA-EVENT. The interval timer 372 times the PEI, and is based on one ormore prior cardiac cycles (or from a data set empirically derived for agiven patient) and does not depend on sensing of a depolarization in theother ventricle (i.e., V1) prior to delivery of the pace at V2 duringpre-excitation fusion-based pacing therapy delivery according to thepresent invention.

The post-event timers 374 time out the post-ventricular time periodsfollowing an RV-EVENT or LV-EVENT or a RV-TRIG or LV-TRIG andpost-atrial time periods following an A-EVENT or A-TRIG. The durationsof the post-event time periods may also be selected as programmableparameters stored in the microcomputer 302. The post-ventricular timeperiods include the PVARP, a post-atrial ventricular blanking period(PAVBP), a ventricular blanking period (VBP), and a ventricularrefractory period (VRP). The post-atrial time periods include an atrialrefractory period (ARP) during which an A-EVENT is ignored for thepurpose of resetting any AV delay, and an atrial blanking period (ABP)during which atrial sensing is disabled. It should be noted that thestarting of the post-atrial time periods and the AV delays can becommenced substantially simultaneously with the start or end of eachA-EVENT or A-TRIG or, in the latter case, upon the end of the A-PACEwhich may follow the A-TRIG. Similarly, the starting of thepost-ventricular time periods and the V-A escape interval can becommenced substantially simultaneously with the start or end of theV-EVENT or V-TRIG or, in the latter case, upon the end of the V-PACEwhich may follow the V-TRIG. The microprocessor 304 also optionallycalculates AV delays, post-ventricular time periods, and post-atrialtime periods that vary with the sensor based escape interval establishedin response to the RCP(s) and/or with the intrinsic atrial rate.

The output amplifiers circuit 340 contains a RA pace pulse generator(and a LA pace pulse generator if LA pacing is provided), a RV pacepulse generator, and a LV pace pulse generator or corresponding to anyof those presently employed in commercially marketed cardiac pacemakersproviding atrial and ventricular pacing. In order to trigger generationof an RV-PACE or LV-PACE pulse, digital controller/timer circuit 330generates the RV-TRIG signal at the time-out of the A-RVP delay (in thecase of RV pre-excitation) or the LV-TRIG at the time-out of the A-LVPdelay (in the case of LV pre-excitation) provided by AV delay intervaltimer 372 (or the V-V delay timer 366). Similarly, digitalcontroller/timer circuit 330 generates an RA-TRIG signal that triggersoutput of an RA-PACE pulse (or an LA-TRIG signal that triggers output ofan LA-PACE pulse, if provided) at the end of the V-A escape intervaltimed by escape interval timers 370.

The output amplifiers circuit 340 includes switching circuits forcoupling selected pace electrode pairs from among the lead conductorsand the IND_CAN electrode 20 to the RA pace pulse generator (and LA pacepulse generator if provided), RV pace pulse generator and LV pace pulsegenerator. Pace/sense electrode pair selection and control circuit 350selects lead conductors and associated pace electrode pairs to becoupled with the atrial and ventricular output amplifiers within outputamplifiers circuit 340 for accomplishing RA, LA, RV and LV pacing.

The sense amplifiers circuit 360 contains sense amplifiers correspondingto any of those presently employed in contemporary cardiac pacemakersfor atrial and ventricular pacing and sensing. As noted in theabove-referenced, commonly assigned, '324 patent, it has been common inthe prior art to use very high impedance P-wave and R-wave senseamplifiers to amplify the voltage difference signal which is generatedacross the sense electrode pairs by the passage of cardiacdepolarization wavefronts. The high impedance sense amplifiers use highgain to amplify the low amplitude signals and rely on pass band filters,time domain filtering and amplitude threshold comparison to discriminatea P-wave or R-wave from background electrical noise. Digitalcontroller/timer circuit 330 controls sensitivity settings of the atrialand ventricular sense amplifiers 360.

The sense amplifiers are uncoupled from the sense electrodes during theblanking periods before, during, and after delivery of a pace pulse toany of the pace electrodes of the pacing system to avoid saturation ofthe sense amplifiers. The sense amplifiers circuit 360 includes blankingcircuits for uncoupling the selected pairs of the lead conductors andthe IND_CAN electrode 20 from the inputs of the RA sense amplifier (andLA sense amplifier if provided), RV sense amplifier and LV senseamplifier during the ABP, PVABP and VBP. The sense amplifiers circuit360 also includes switching circuits for coupling selected senseelectrode lead conductors and the IND_CAN electrode 20 to the RA senseamplifier (and LA sense amplifier if provided), RV sense amplifier andLV sense amplifier. Again, sense electrode selection and control circuit350 selects conductors and associated sense electrode pairs to becoupled with the atrial and ventricular sense amplifiers within theoutput amplifiers circuit 340 and sense amplifiers circuit 360 foraccomplishing RA, LA, RV and LV sensing along desired unipolar andbipolar sensing vectors.

Right atrial depolarizations or P-waves in the RA-SENSE signal that aresensed by the RA sense amplifier result in a RA-EVENT signal that iscommunicated to the digital controller/timer circuit 330. Similarly,left atrial depolarizations or P-waves in the LA-SENSE signal that aresensed by the LA sense amplifier, if provided, result in a LA-EVENTsignal that is communicated to the digital controller/timer circuit 330.Ventricular depolarizations or R-waves in the RV-SENSE signal are sensedby a ventricular sense amplifier result in an RV-EVENT signal that iscommunicated to the digital controller/timer circuit 330. Similarly,ventricular depolarizations or R-waves in the LV-SENSE signal are sensedby a ventricular sense amplifier result in an LV-EVENT signal that iscommunicated to the digital controller/timer circuit 330. The RV-EVENT,LV-EVENT, and RA-EVENT, LA-SENSE signals may be refractory ornon-refractory, and can inadvertently be triggered by electrical noisesignals or aberrantly conducted depolarization waves rather than trueR-waves or P-waves.

To simplify the description of FIGS. 4 through 6, it will be assumedthat the following references to an “A-EVENT” and “A-PACE” will denoteright atrial activity. In the event that the left atrium is monitored(or stimulated), the reader should appreciate that the LA is referredto.

Some of the operating modes of IPG circuit 300 according to the presentinvention are depicted in the flow charts (FIGS. 4-6) and described asfollows. The particular operating mode of the present invention is aprogrammed or hardwired sub-set of the possible operating modes as alsodescribed below. For convenience, the algorithm of FIGS. 4-6 isdescribed in the context of determining the PEI delay and computing theA-V2p intervals to optimally pace the V2 chamber to produceelectromechanical fusion with the corresponding intrinsic depolarizationof the V1 chamber. The V1 chamber depolarizes intrinsically so that thepre-excited electromechanical fusion occurs as between the intrinsicallyactivated V1 chamber and the pre-excitation evoked response of the V2chamber. As noted below, the algorithm can be employed to determine anoptimal PEI delay that results in an A-V2p interval producingventricular synchrony (i.e., CRT delivery via a single ventricularpacing stimulus). Of course, the methods according to the presentinvention are intended to be stored as executable instructions on anyappropriate computer readable medium although they may be performedmanually as well.

FIG. 4 illustrates one embodiment of the present invention wherein theIPG circuit 300 includes a method 400 beginning with step S402 that isperiodically performed to determine the intrinsic ventricular delaybetween the LV and the RV. In step 402 the first-to-depolarize ventricleis labeled V1 and the second-to-depolarize ventricle is labeled V2 andthe corresponding shortest A-V interval is stored as the “A-V1” delayinterval. In step 404 the A-V1 delay interval is decremented by the PEIto generate the A-V2p interval for delivering pacing stimulus to the V2chamber. The magnitude of the PEI depends on several factors, includinginternal circuitry processing delay, location of sensing electrodes,location of pacing electrodes, heart rate, dynamic physiologicconduction status (e.g., due to ischemia, myocardial infarction, LBBB orRBBB, etc.). However, the inventors have found that a PEI ofapproximately 20-40 milliseconds (ms) oftentimes provides adequatepre-excitation to the V2 chamber resulting in electromechanical fusionof both ventricles. However, a reasonable range for the PEI runs fromabout one ms to about 100 ms (or more). Of course, an iterativesubroutine for decrementing the A-V1 delay can be used and/or a clinicalprocedure utilized to help narrow a range of prospective values for themagnitude of the decrease in the A-V1 delay. According to this part ofthe present invention a series of decrements are implemented over aseries of at least several cardiac cycles (as needed for the hemodynamicor contractile response to stabilize). The hemodynamic response can begauged with external or internal sensors (e.g., surface ECG,intracardiac EGM, internal or endocardial pressure sensor, epicardialaccelerometer, arterial flow sensor, etc.). Doppler echocardiography orultrasound techniques may also be used to confirm the appropriatedecrement of the A-V1 delay.

In another aspect, a data set is generated for a range of heart ratesthat correspond to measured A-V1 (and/or A-V2) delay intervals. The datamay include paced or intrinsic heart rate data (ppm and bpm,respectively). In this aspect of the invention, the data set can beemployed as a guiding or a controlling factor during heart rateexcursions for continuous delivery of the single ventricularpre-excitation pacing of the present invention. In one form of thisaspect of the invention, internal physiologic sensor data may be used asa guiding factor when determining an appropriate setting for the PEI(A-V2).

In yet another aspect, a first data set of appropriate values of theA-V2 delay interval are based on evoked response (i.e., wherein theA-EVENT is a pacing event) and a second data set of appropriate valuesof the A-V2 delay interval are based on intrinsic response (i.e.,wherein the A-EVENT is a natural atrial depolarization).

Following the decrementing step 404 the A-V2p (pacing) delay interval isset and in step 406 pre-excitation pacing therapy is delivered to the V2chamber upon expiration of the A-V1 p interval.

In the presently illustrated embodiment of the invention, pre-excitationpacing therapy delivery continues until: a pre-set number of cardiaccycles occur, a pre-set time period expires, a loss of capture occurs inthe V2 chamber, or a physiologic response trigger event occurs. Thephysiologic response trigger will be described below. With respect tothe other three situations, the number of cardiac cycles or the timeperiod may be set to any clinically appropriate value, given thepatient's physiologic condition (among other factors) before returningto step 402 and (re-)determining the physiologic A-V1 interval andderiving an operating PEI (A-V2p). If a loss of capture in the V2chamber is detected it could indicate that the V2p (pacing) stimulus isbeing delivered too late (e.g., during the refractory period of the V2chamber) or that the V2 pacing electrodes have malfunctioned or becomedislodged. While the process 400 depicted in FIG. 4 reflect that underall the foregoing situations steps 402-406 should be performed followingevents (i)-(iii), the pre-excitation pacing therapy could of course bediscontinued or a mode switch could be performed to another pacingmodality (e.g., an AAI, ADI, AAI/R, ADI/R, double chamber DDD or DDD/R,and the like).

With respect to the physiologic response trigger event(s)—as well asoptionally with respect to condition (iii) wherein loss of capture ofthe V2 chamber occurs due to inappropriate timing of the V2 pacingstimulus—at step 410 an iterative closed-loop process for determining anappropriate A-V2p interval is performed. In step 410, the A-V2p intervalis directly manipulated from a prior operating value while one or morephysiologic response is monitored and/or measured and stored. Asmentioned above with respect to step 404 with regard to decrementing theintrinsic A-V1 interval to generate the operating A-V2p interval, anumber of sensors may be employed. After storing the physiologicresponse data (and corresponding PEI used during data collection) atstep 412 the data is compared and the PEI corresponding to the mostfavorable physiologic response is then programmed as the operating PEI.The process then proceeds back to step 406 and the V2 chamber receivespre-excitation pacing therapy upon the expiration of thephysiologically-derived PEI. Of course, of the foregoing steps, steps402,404,406 may be performed wherein step 402 (deriving the PEI fromA-V1 interval) is only performed occasionally (e.g., every ten cardiaccycles, during heart rate excursions, etc.). In this form of theinvention, the magnitude of the decrement of the A-V1, or the PEIitself, can be based upon one or more prior operating PEI value (andseveral prior operating PEI values, with the most recent PEI receivingadditional statistical weighting). In addition to or in lieu of theforegoing a look up table (LUT) or other data compilation, as describedabove, may be utilized to guide or control the derivation of the PEIvalue (as described in more detail with respect to FIG. 5).

Now turning to FIG. 5, another embodiment of a method according to thepresent invention is depicted as process 500. To begin process 500, thesteps 502,504,506,508 correspond closely to the corresponding steps ofprocess 400 (FIG. 4) just described. However, at step 510—in the eventthat condition (iv) of step 508 is declared—a data set (or LUT) ofphysiologic responses and corresponding PEI values for a given patientis accessed. At step 512 the PEI is programmed to a value correspondingto the current physiologic response trigger for the patient. Then, atstep 506, pre-excitation pacing ensues upon expiration of the newlyprogrammed PEI. A representative physiologic response trigger includesan upward or downward heart rate excursion, a sensed lack of ventricularsynchrony (based on accelerometer, pressure, EGM or other physiologicdata signals) and the like.

In FIG. 6, a process 600 for periodically ceasing delivery of thepre-excitation, single ventricular pacing therapy to perform a pacingmode switch to a different form of pre-excitation therapy, ceasingpre-excitation therapy, or allowing normal sinus rhythm to continue(chronically) is illustrated. The process 600 can be implemented as apart of steps 402,502 (or process 400 and 500, respectively) fordetermining the intrinsic A-V1 interval or can be performedindependently. In either case, process 600 is designed to help revealimprovement (or decline) of a patient's condition. In the former case,if so-called “reverse remodeling” of the myocardium occurs resulting inreturn of ventricular synchrony and improved hemodynamics and autonomictone, pre-excitation therapy delivery may be temporarily or permanentlyterminated. The patient may, in the best scenario, be relieved of pacingtherapy delivery altogether (programming the pacing circuitry to an ODOmonitoring-only “pacing modality”). Assuming the patient is notchronotropically incompetent, normal sinus rhythm may emerge permanentlyfor all the activities of daily living. Additionally, the process 600may be employed to search for a change in conduction status (e.g.,wherein V2 changes from LV to RV, or wherein A-V1 conduction timingchanges, etc.). According to process 600, at step 602 the delivery ofpre-excitation therapy ceases and for at least one cardiac cycle theintrinsic, normal sinus rhythm is allowed to emerge. At step 604 thedepolarization(s) of the LV and RV are monitored (and, optionally storedin memory). At step 606 a comparison of the depolarization timing iscompared and at decision step 608 three outcomes are determined based onthe comparison of depolarization timing. If the RV depolarization occursprior to the LV depolarization then step 610 is performed wherein the LVcomprises the V2 chamber and A-LVP pre-excitation is initiated(according to process 400 or 500 or analogues thereof). However, if theLV depolarization occurs prior to the RV depolarization then step 612 isperformed wherein the RV comprises the V2 chamber and A-RVPpre-excitation is initiated (according to process 400 or 500 oranalogues thereof). Finally, if the RV depolarization occurssubstantially at the same time as the LV depolarization then step 614 isperformed. In step 614, either normal sinus rhythm is allowed tocontinue or a non-pre-excitation pacing therapy is initiated. Someexamples of such therapy include: AAI, AAI/R, ADI, ADI/R, double chamberDDD, DDD/R and bi-ventricular pacing, and the like.

In addition to or in lieu of the subject matter described above (inparticular with respect to FIG. 5 and FIG. 6), fusion pacing can besuspended for one or more cardiac cycles while V1 depolarization(s) aremonitored. Also, a form of CRT delivery could be implemented wherein theV2 pacing therapy delivery is triggered off a sensed (intrinsic)depolarization of the V1 chamber. The latter technique allows collectionof intrinsic A-V1 timing while still preserving some of the hemodynamicbenefit of CRT delivery. In addition, the intra-ventricular conductiontime (IVCT) can be measured and used to assist calculate appropriatetiming according to the invention. The IVCT could be measured between a(relatively early) pacing stimulus delivered to the V1 chamber andsensing the conduction time until the V2 chamber depolarizes (and viceversa). Furthermore, since the electrodes disposed in the V1 chamber areprimarily, if not exclusively, only sensing intrinsic ventricularactivity said electrodes can be programmed with very short blankingperiods and thus used to measure so-called “far-field” R-waves from theV2 chamber.

It should be understood that, certain of the above-described structures,functions and operations of the pacing systems of the illustratedembodiments are not necessary to practice the present invention and areincluded in the description simply for completeness of an exemplaryembodiment or embodiments. It will also be understood that there may beother structures, functions and operations ancillary to the typicaloperation of an implantable pulse generator that are not disclosed andare not necessary to the practice of the present invention.

In addition, it will be understood that specifically describedstructures, functions and operations set forth in the above-referencedpatents can be practiced in conjunction with the present invention, butthey are not essential to its practice. It is therefore to beunderstood, that within the scope of the appended claims, the inventionmay be practiced otherwise than as specifically described withoutactually departing from the spirit and scope of the present invention.

1. A method of left ventricular pacing including automated adjustment of a atrio-ventricular (AV) pacing delay interval and intrinsic AV nodal conduction testing comprising—upon expiration or reset of a programmable AV Evaluation Interval (AVEI)—performing the following steps: temporarily increasing a paced AV (PAV) interval and a sensed AV (SAV) interval and a. testing for adequate AV conduction and b. measuring a median intrinsic atrio-ventricular (PR) interval for a first-to-depolarize ventricular chamber for at least three consecutive cardiac cycles, storing: in the event that the AV conduction test reveals a physiologically acceptable intrinsic PR interval for said ventricular chamber then storing the physiologically acceptable median PR interval in a memory structure; subtracting approximately 30 milliseconds from the median PR interval to define a pre-excitation interval (PEI); in the event that the AV conduction test reveals unacceptably long PR intervals then:
 1. performing a pacing mode-switch to a bi-ventricular (Bi-V) pacing mode and
 2. increasing the magnitude of the AVEI; and delivering a pacing stimulus to the last to depolarize ventricle approximately at the expiration of the PEI.
 2. A method according to claim 1, further comprising calculating an FAV delay interval for paced atrial events (F-PAV interval) and for sensed atrial events (F-SAV interval) and storing at least one of the F-PAV interval and the F-SAV interval in a first-in-first-out memory buffer.
 3. A method according to claim 1, further comprising: delivering a single pacing stimulus to a left ventricular (LV) chamber at the expiration of the FAV delay interval.
 4. A method according to claim 1, wherein the AVEI comprises one of a temporal unit and a number of cardiac cycles.
 5. A method according to claim 1, wherein the AVEI expires or is adjusted based upon one of: a detected level of activity of a patient, a heart rate of the patient, a rate of change of the heart rate of the patient.
 6. A method according to claim 2, wherein the step of calculating an FAV delay interval for paced atrial events is based on the SAV interval is performed according to the mathematical relationship: A _(sp) CO=(A _(p)-RV _(s))−(A _(s)-RV _(s)) wherein A_(sp)CO stands for an Atrial Sense/Atrial Pace Conduction Offset value.
 7. A method according to claim 6, further comprising periodically updating the A_(sp)CO value.
 8. A method according to claim 1, further comprising: immediately halting the performance of the claimed method based on satisfaction of one of a preselected criteria and predetermined condition; and performing a pacing mode-switch to a bi-ventricular (Bi-V) pacing therapy.
 9. A method according to claim 8, wherein one of the preselected criteria and the predetermined condition comprises: a detection of a tachycardia episode, an occurrence of the tachycardia episode, a probability of the tachycardia episode, a detection of an arrhythmia, an AV conduction block condition, a prolonged AV conduction condition.
 10. A method according to claim 9, wherein the tachycardia episode comprises one of a ventricular tachycardia episode and a ventricular fibrillation episode.
 11. A method according to claim 8, wherein subsequent to one of the preselected criteria and the predetermined condition being satisfied waiting for a nominal interval and then performing at least one of the following: performing the method of claim 1 without utilizing any prior temporal values; delay at least one AVEI and attempt to perform the method of claim 1; in the event that a programmable period of time has expired, then switching to Bi-V pacing therapy; and adjusting a PVARP blanking interval for a programmable period of time.
 12. A method according to claim 1, further comprising: wherein one of the rate of change and the magnitude of change from a prior FAV delay interval to a new FAV delay interval are constrained to a programmable increment.
 13. A method according to claim 12, wherein the programmable increment comprises between about five milliseconds and about thirty milliseconds.
 14. A method according to claim 1, further comprising: delivering a ventricular pacing pulse following a predetermined period of time during the AV conduction test.
 15. A method according to claim 14, wherein the pacing pulse is delivered at approximately 350 ms following detection of an atrial event. 